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1.
J Asian Nat Prod Res ; : 1-18, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287960

RESUMEN

This study aimed to investigate the effects of wild Cordyceps sinensis on chronic obstructive pulmonary disease (COPD) rats through metabolomics approach, combined with biochemical parameters evaluations. Consequently, C. sinensis exhibited regulatory effects on the lung's metabolic profiles in COPD rats. Treatment with C. sinensis potentially modulated glycerophospholipid metabolism, glutathione metabolism, and tryptophan metabolism, thereby alleviating oxidative stress (by decreasing MDA and GSSG, while increasing SOD and GSH) and inflammatory response (by inhibiting TNF-α, IL-8, and MMP-9) in COPD rats while improving lung tissue damage.

2.
Huan Jing Ke Xue ; 45(7): 3839-3848, 2024 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-39022932

RESUMEN

In order to control the increasing ozone (O3) pollution in Hebi, Henan Province, clarifying the pollution characteristics of ozone and its precursors is vital. Therefore, we conducted a comprehensive analysis of O3 pollution utilizing the OFP-PMF-EKMA method combined with online hourly resolution monitoring data of conventional pollutants and volatile organic compounds (VOCs) in the summer of 2022 (June-September). Ozone formation potential (OFP) was used to identify the key VOCs species, and the PMF model was used to identify the VOCs emission sources, whereas EKMA curves and scenario analysis were used to identify the main ozone control area in Hebi and to determine the reduction ratio of VOCs and NOx in a scientifically refined way. In 2022, Hebi had persistent O3 pollution, with the highest concentration in June. Conditions of high temperature, low humidity, and low atmospheric pressure contributed to the O3 accumulation. Aromatic and oxygenated volatile organic compounds (OVOCs) contributed significantly to the OFP and VOCs fraction, which were the dominant active substance and concentration dominant species. The results of the VOCs source analysis indicated that vehicle exhaust sources (25.3%) were the main source of atmospheric VOCs, followed by process sources (17.7%) and biomass combustion sources (17.6%). Thus, emission sources associated with the combustion of fossil fuels and industrial production emissions were the most urgent sources of atmospheric VOCs to be controlled in Hebi. The O3 generation in Hebi occurred in the VOCs-sensitive zones, and the emission reduction results showed that a synergistic emission reduction of VOCs and nitrogen oxide (NOx) could effectively control O3 pollution with a 75% reduction in VOCs and a 10% reduction in NOx.

3.
CNS Drugs ; 38(7): 547-558, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38573471

RESUMEN

BACKGROUND: Percutaneous endoscopic transforaminal discectomy (PETD) is an effective method for treating lumbar disc herniation, and is typically performed under local anesthesia. However, inadequate analgesia during the procedure remains a concern, prompting the search for a medication that can provide optimal pain control with minimal impact on the respiratory and circulatory systems. OBJECTIVES: The aim of this study was to observe the effects of different doses of esketamine combined with dexmedetomidine on reducing visual analog scale (VAS) scores during surgical interventions. METHODS: One hundred two patients who underwent PETD were randomly divided into a control group (group C: normal saline + dexmedetomidine), an E1 group (0.1 mg kg-1 esketamine + dexmedetomidine), and an E2 group (0.2 mg kg-1 esketamine + dexmedetomidine). The primary outcome was the maximum visual analogue scale (VAS) (score: 0 = no pain and 10 = worst pain) at six time points. The secondary outcomes included the Assessment of Alertness/Sedation Scale (OAA/S) score and mean arterial pressure (BP), heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) at 11 time points. The incidence of adverse reactions during and 24 h after the operation and patient satisfaction with the anesthesia were also recorded. RESULTS: Compared with those in group C, the VAS scores of patients in groups E1 and E2 were lower at T6, T7, and T9 (P < 0.05). From T4 to T10, the OAA/S scores of the E1 and E2 groups were both lower than those of group C (P < 0.05), and at the T4-T6 time points, the OAA/S score of the E2 group was lower than that of group E1 (P < 0.05). At T4 and T5, the HR and BP of patients in groups E1 and E2 were greater than those in group C (P < 0.05). Compared with those in group C, the incidences of intraoperative illusion, floating sensation, postoperative dizziness, and hyperalgesia in groups E1 and E2 were significantly greater (P < 0.01). There was no significant difference in patient RR, SpO2, or postoperative satisfaction with anesthesia among the three groups (P > 0.05). CONCLUSION: The combination of esketamine and dexmedetomidine can reduce VAS scores during certain stages of this type of surgery; it has minimal impact on respiration and circulation. However, this approach is associated with increased incidences of postoperative dizziness and psychiatric side effects, which may also affect patients' compliance with surgical instructions from medical staff. Patient satisfaction was not greater with dexmedetomidine combined with esketamine than with dexmedetomidine alone. TRIAL REGISTRATION: http://www.chictr.org.cn . Identifier: ChiCTR2300068206. Date of registration: 10 February 2023.


Asunto(s)
Dexmedetomidina , Discectomía Percutánea , Desplazamiento del Disco Intervertebral , Ketamina , Humanos , Dexmedetomidina/administración & dosificación , Femenino , Masculino , Método Doble Ciego , Ketamina/administración & dosificación , Adulto , Persona de Mediana Edad , Desplazamiento del Disco Intervertebral/cirugía , Discectomía Percutánea/métodos , Analgésicos/administración & dosificación , Quimioterapia Combinada , Dimensión del Dolor , Relación Dosis-Respuesta a Droga , Endoscopía/métodos , Dolor Postoperatorio/tratamiento farmacológico , Resultado del Tratamiento , Vértebras Lumbares/cirugía
4.
Transl Pediatr ; 13(2): 260-270, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38455752

RESUMEN

Background: Timely and accurate pathogen diagnosis can be challenging in children who contract a respiratory virus following congenital heart surgery (CHS). This often results in suboptimal drug use and treatment delays. Metagenomics next-generation sequencing (mNGS) is a swift, efficient, and unbiased method for obtaining microbial nucleic acid sequences. This technology holds promise as a comprehensive diagnostic tool, especially for pathogens undetectable by traditional methods. However, the efficacy of mNGS in the context of congenital heart disease infections remains uncertain. This study aimed to explore the diagnostic value of mNGS for respiratory virus infections post-CHS. Methods: We conducted a retrospective analysis of patients who developed respiratory tract infections post-CHS and were admitted to our cardiac center between July 2021 and December 2022. The patients were categorized into the following two groups based on the diagnostic method used: (I) the mNGS group (comprising 62 patients); and (II) the conventional microbiological test (CMT) group (comprising 70 patients). Bronchoalveolar lavage fluid (BALF) samples from these patients were tested to identify pathogens. Results: The mNGS group had significantly higher detection rates for both viral infections and mixed viral infections than the CMT group (56.45% vs. 17.14%, P<0.001, and 80.00% vs. 16.67%, P<0.001, respectively). In the mNGS group, 19.35% of the patients received antiviral therapy, and 61.29% received an anti-infective regimen adjustment. Conversely, in the CMT group, only 4.29% received antiviral therapy, and 28.57% received an anti-infective regimen adjustment. A higher percentage of patients showed improved respiratory symptoms in the mNGS group than the CMT group (74.19% vs. 44.29%, P=0.001). Additionally, the mNGS group had a shorter duration of mechanical ventilation and a reduced length of stay in the cardiac intensive care unit than the CMT group (P=0.012). Conclusions: Using mNGS for BALF enhances the detection of respiratory viral infections and coexisting viral infections post-CHS. This facilitates more precise treatment strategies and could potentially lead to improved patient outcomes.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38524397

RESUMEN

Purpose: Circular RNAs (circRNAs) are newly identified endogenous non-coding RNAs that function as crucial gene modulators in the development of several diseases. By assessing the expression levels of circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD), this study attempted to find new biomarkers for COPD screening. Patients and Methods: We confirmed altered circRNA expression in PBMCs of COPD (n=41) vs controls (n=29). Further analysis focused on the highest and lowest circRNA expression levels. The T-test is used to assess the statistical variances in circRNAs among COPD patients in the smoking and non-smoking cohorts. Additionally, among smokers, the Spearman correlation test assesses the association between circRNAs and clinical indicators. Results: Two circRNAs, hsa_circ_0042590 and hsa_circ_0049875, that were highly upregulated and downregulated in PBMCs from COPD patients were identified and verified. Smokers with COPD had lower hsa_circ_0042590 and higher hsa_circ_0049875, in comparison to non-smokers. There was a significant correlation (r=0.52, P<0.01) between the number of acute exacerbations (AEs) that smokers with COPD experienced in the previous year and the following year (r=0.67, P<0.001). Moreover, hsa_circ_0049875 was connected to the quantity of AEs in the year prior (r=0.68, P<0.0001) as well as the year after (r=0.72, P<0.0001). AUC: 0.79, 95% CI: 0.1210-0.3209, P<0.0001) for hsa_circ_0049875 showed a strong diagnostic value for COPD, according to ROC curve analysis. Hsa_circ_0042590 showed a close second with an AUC of 0.83 and 95% CI: -0.1972--0.0739 (P <0.0001). Conclusion: This research identified a strong correlation between smoking and hsa_circ_0049875 and hsa_circ_0042590 in COPD PBMCs. The number of AEs in the preceding and succeeding years was substantially linked with the existence of hsa_circ_0042590 and hsa_circ_0049875 in COPD patients who smoke. Additionally, according to our research, hsa_circ_0049875 and hsa_circ_0042590 may be valuable biomarkers for COPD diagnosis.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , ARN Circular , Humanos , ARN Circular/genética , Leucocitos Mononucleares/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Biomarcadores/metabolismo
6.
BMC Pulm Med ; 24(1): 92, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383357

RESUMEN

OBJECTIVE: To evaluate the efficacy of high-flow nasal cannula oxygenation (HFNC) versus non-invasive ventilation (NIV) in pediatric patients post-congenital heart surgery (CHS) through a meta-analysis. METHODS: A comprehensive literature search was conducted across the Chinese biomedical literature database, Vip database, CNKI, Wanfang, PubMed, Embase, Cochrane Library, and Web of Science until December 20, 2022. We selected RCTs or cohort studies that met inclusion criteria for a meta-analysis using RevMan 5.4 software. RESULTS: Our search yielded five publications, comprised of one randomized controlled trial and four cohort studies. Meta-analysis revealed a significant reduction in reintubation rates in children post-CHS treated with HFNC as compared to NIV [RR = 0.36, 95%CI(0.25 ~ 0.53), P < 0.00001]. There was also a notable reduction in the duration of ICU stay [MD = -4.75, 95%CI (-9.38 ~ -0.12), P = 0.04]. No statistically significant differences were observed between HFNC and NIV in terms of duration of mechanical ventilation, 24 h PaO2, and PaCO2 post-treatment (P > 0.05). Furthermore, both groups showed no significant difference in the duration of extracorporeal circulation [MD = -8.27, 95%CI(-17.16 ~ 0.62), P = 0.07]. CONCLUSIONS: For pediatric patients post-CHS, HFNC appears to be more effective than NIV in reducing reintubation rates and shortening the CICU stay.


Asunto(s)
Cánula , Procedimientos Quirúrgicos Cardíacos , Cardiopatías Congénitas , Ventilación no Invasiva , Terapia por Inhalación de Oxígeno , Humanos , Ventilación no Invasiva/métodos , Procedimientos Quirúrgicos Cardíacos/métodos , Terapia por Inhalación de Oxígeno/métodos , Cardiopatías Congénitas/cirugía , Tiempo de Internación/estadística & datos numéricos , Niño , Cuidados Posoperatorios/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
Ecotoxicol Environ Saf ; 270: 115907, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38176185

RESUMEN

Fluoride has strong electronegativity and exposes diversely in nature. Water fluoridation is the most pervasive form of occurrence, representing a significant threat to human health. In this study, we investigate the morphometric and physiological alterations triggered by fluoride stimulation during the embryogenesis of zebrafish and reveal its putative effects of stage- and/or dose-dependent. Fluoride exhibits potent biological activity and can be extensively absorbed by the yolk sac, exerting significant effects on the development of multiple organs. This is primarily manifested as restricted nutrient utilization and elevated levels of lipid peroxidation, further leading to the accumulation of superoxide in the yolk sac, liver, and intestines. Moreover, pericardial edema exerts pressure on the brain and eye development, resulting in spinal curvature and reduced body length. Besides, acute fluoride exposure with varying concentrations has led to diverse teratogenic outcomes. A low dose of water fluoridation tends to induce abnormal development of the embryonic yolk sac, while vascular malformation is widely observed in all fluoride-treated groups. The effect of fluoride exposure on blood circulation is universally present, even in zebrafish larvae that do not exhibit obvious deformities. Their swimming behavior is also affected by water fluoridation, resulting in reduced activity and delayed reactions. In conclusion, this study provides valuable insights into the monitoring of environmental quality related to water fluoridation and disease prevention.


Asunto(s)
Contaminantes Químicos del Agua , Pez Cebra , Animales , Humanos , Fluoruros/toxicidad , Fluoruración , Desarrollo Embrionario , Saco Vitelino , Embrión no Mamífero , Contaminantes Químicos del Agua/toxicidad
8.
Huan Jing Ke Xue ; 45(1): 115-122, 2024 Jan 08.
Artículo en Chino | MEDLINE | ID: mdl-38216463

RESUMEN

Ships are important sources of carbon dioxide (CO2) emissions in Guangdong Province. The study of historical evolutions, drivers, and projected pathways of CO2 emissions can provide scientific support for the development of carbon peaking and carbon neutral strategies in Guangdong Province. The emission factor method, log-average index (LMDI) method, and scenario analysis method were adopted to estimate CO2 emissions, identify the drivers, and explore the mitigation potential from ships in Guangdong Province, separately. The results showed that:① CO2 emissions from ships in Guangdong Province increased from 3.319 4 million tons to 6.392 9 million tons from 2006 to 2020, with dry bulk carriers and container ships being the main ship types causing the increase in emissions. ② The positive drivers of CO2 emissions from ships in Guangdong Province from 2006 to 2020 were transport intensity (51%) and economic factors (49%), and the negative drivers were energy intensity (93%) and cargo class structure (7%). ③ Carbon peaking would not be reached by 2030 if Guangdong Province maintains the current policy (baseline scenario) for ship transportation. ④ Simultaneous optimization of the energy structure and promotion of the energy intensity (energy-efficient and low-carbon scenario) had a 56.51% potential to reduce CO2 emissions from ships compared to the baseline scenario. This can provide scientific support for Guangdong Province to develop a carbon peaking and carbon neutral control strategy for the shipping industry.

9.
Int Urol Nephrol ; 56(1): 167-179, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37450241

RESUMEN

As a high energy consumption organ, kidney relies on a large number of mitochondria to ensure normal physiological activities. Under specific stimulation, mitophagy and mitochondrial dynamics (fission, fusion) cooperatively regulate mitochondrial quality and participate in many life activities such as energy metabolism, inflammatory response, oxidative stress, cell senescence and death. Mitophagy plays a key role in the progression of acute kidney injury and chronic kidney disease. The early induction of oxidative stress in renal parenchyma, the activation of pro-inflammatory cytokines and TGF-ß signal pathway are closely related to renal interstitial fibrosis. Macrophage reprogramming is also considered to be an important participant in the progression of kidney fibrosis. This review summarizes the molecular mechanism of mitochondrial autophagy and its relationship with the pathway of promoting fibrosis, and discusses the possibility of restoring mitophagy balance as a pharmacological target for the treatment of renal interstitial fibrosis, so as to provide new ideas for more efficient anti-fibrosis and delay the progress of chronic kidney disease.


Asunto(s)
Lesión Renal Aguda , Insuficiencia Renal Crónica , Humanos , Mitofagia/fisiología , Riñón/patología , Fibrosis , Lesión Renal Aguda/patología , Insuficiencia Renal Crónica/patología
10.
Adv Sci (Weinh) ; 11(7): e2306143, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38083984

RESUMEN

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-ExoLaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-ExoLaIMTS show obvious differences. The AnCar-ExoLaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-ExoLaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.


Asunto(s)
Artritis , Macrófagos , Humanos , Macrófagos/metabolismo , Artritis/tratamiento farmacológico , Fagocitosis , Antiinflamatorios/uso terapéutico , Comunicación Celular
11.
Plant Cell Environ ; 47(3): 799-816, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38111215

RESUMEN

Phosphorus (P) is a crucial macronutrient for plant growth, development, and reproduction. The effects of low P (LP) stress on leaf senescence and the role of PHR1 in LP-induced leaf senescence are still unknown. Here, we report that PHR1 plays a crucial role in LP-induced leaf senescence, showing delayed leaf senescence in phr1 mutant and accelerated leaf senescence in 35S:PHR1 transgenic Arabidopsis under LP stress. The transcriptional profiles indicate that 763 differentially expressed SAGs (DE-SAGs) were upregulated and 134 DE-SAGs were downregulated by LP stress. Of the 405 DE-SAGs regulated by PHR1, 27 DE-SAGs were involved in P metabolism and transport. PHR1 could bind to the promoters of six DE-SAGs (RNS1, PAP17, SAG113, NPC5, PLDζ2, and Pht1;5), and modulate them in LP-induced senescing leaves. The analysis of RNA content, phospholipase activity, acid phosphatase activity, total P and phosphate content also revealed that PHR1 promotes P liberation from senescing leaves and transport to young tissues under LP stress. Our results indicated that PHR1 is one of the crucial modulators for P recycling and redistribution under LP stress, and the drastic decline of P level is at least one of the causes of early senescence in P-deficient leaves.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Fósforo/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Senescencia de la Planta , Factores de Transcripción/metabolismo , Fosfatos/metabolismo , Hojas de la Planta/metabolismo , Homeostasis , Regulación de la Expresión Génica de las Plantas
12.
J Cardiothorac Vasc Anesth ; 38(3): 739-744, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38151455

RESUMEN

OBJECTIVE: The authors aimed to assess the relationship between elevated renal-resistive index (RRI) and acute kidney injury (AKI) related to extracorporeal membrane oxygenation (ECMO) in neonatal patients. DESIGN: This was a retrospective study. SETTING: The study was conducted at a teaching hospital. PARTICIPANTS: Sixteen neonates treated with ECMO at the authors' hospital between June 2021 and December 2022 were included in this study. INTERVENTIONS: Demographic and clinical data of patients were collected from the computer database. The RRI of patients before and during ECMO treatment was measured by bedside ultrasound. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of elevation of RRI as evidence of neonatal ECMO-related AKI. Logistic regression analysis was utilized to calculate the odds ratio (OR) with a 95% CI. MEASUREMENTS AND MAIN RESULTS: A total of 16 patients met the inclusion criteria. For the primary outcome, the authors observed that the RRI during ECMO therapy was significantly elevated in patients with AKI compared to those without AKI. As for the secondary outcome, ROC curve analysis revealed an optimal RRI cutoff of 0.797, with an area under the curve of 0.855 (95% CI, 0.664-1, p = 0.027). The sensitivity and specificity of RRI values >0.797 for diagnosing AKI were 72.7% and 80%, respectively. Univariate logistic regression analysis indicated an OR of 1.433 (95% CI 1.192-1.873, p < 0.05) for RRI values above 0.797. This association remained statistically significant even after adjusting for serum cystatin C and Sequential Organ Failure Assessment score, with an adjusted OR of 1.352 (95% CI 1.108-1.612, p < 0.05). CONCLUSION: The elevation of the RRI demonstrated a strong correlation with the onset of neonatal ECMO-related AKI, which may offer valuable support for diagnosing neonatal ECMO-related AKI.


Asunto(s)
Lesión Renal Aguda , Oxigenación por Membrana Extracorpórea , Recién Nacido , Humanos , Oxigenación por Membrana Extracorpórea/efectos adversos , Estudios Retrospectivos , Estudios Prospectivos , Riñón , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia
13.
Front Pharmacol ; 14: 1228895, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37781698

RESUMEN

Ketamine is a racemic mixture of equal amounts of R-ketamine and S-ketamine and is well known to anesthesiologists for its unique dissociative anesthetic properties. The pharmacological properties of ketamine, namely, its sympathetic excitation, mild respiratory depression, and potent analgesia, are still highly valued in its use as an anesthetic for some patients. In particular, since its advent, S-ketamine has been widely used as an anesthetic in many countries due to its increased affinity for NMDA receptors and its enhanced anesthetic and analgesic effects. However, the anesthetic and analgesic mechanisms of S-ketamine are not fully understood. In addition to antagonizing NMDA receptors, a variety of other receptors or channels may be involved, but there are no relevant mechanistic summaries in the literature. Therefore, the purpose of this paper is to review the mechanisms of action of S-ketamine on relevant receptors and systems in the body that result in its pharmacological properties, such as anesthesia and analgesia, with the aim of providing a reference for its clinical applications and research.

14.
FASEB J ; 37(11): e23221, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37795761

RESUMEN

Ubiquitin fold modifier 1 is a small ubiquitin-like protein modifier that is essential for embryonic development of metazoans. Although UFMylation has been connected to endoplasmic reticulum homeostasis, the underlying mechanisms and the relevant cellular targets are largely unknown. Here, we show that HRD1, a ubiquitin ligase of ER-associated protein degradation (ERAD), is a novel substrate of UFM1 conjugation. HRD1 interacts with UFMylation components UFL1 and DDRGK1 and is UFMylated at Lys610 residue. In UFL1-depleted cells, the stability of HRD1 is increased and its ubiquitination modification is reduced. In the event of ER stress, the UFMylation and ubiquitination modification of HRD1 is gradually inhibited over time. Alteration of HRD1 Lys610 residue to arginine impairs its ability to degrade unfolded or misfolded proteins to disturb protein processing in ER. These results suggest that UFMylation of HRD1 facilitates ERAD function to maintain ER homeostasis.


Asunto(s)
Estrés del Retículo Endoplásmico , Ubiquitina-Proteína Ligasas , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Estrés del Retículo Endoplásmico/fisiología , Proteínas/metabolismo , Retículo Endoplásmico/metabolismo , Ubiquitina/metabolismo , Homeostasis , Degradación Asociada con el Retículo Endoplásmico
15.
Int J Mol Sci ; 24(19)2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37834012

RESUMEN

Triple-negative breast cancer (TNBC) is the most fatal subtype of breast cancer; however, effective treatment strategies for TNBC are lacking. Therefore, it is important to explore the mechanism of TNBC metastasis and identify its therapeutic targets. Dysregulation of ETHE1 leads to ethylmalonic encephalopathy in humans; however, the role of ETHE1 in TNBC remains elusive. Stable cell lines with ETHE1 overexpression or knockdown were constructed to explore the biological functions of ETHE1 during TNBC progression in vitro and in vivo. Mass spectrometry was used to analyze the molecular mechanism through which ETHE1 functions in TNBC progression. ETHE1 had no impact on TNBC cell proliferation and xenograft tumor growth but promoted TNBC cell migration and invasion in vitro and lung metastasis in vivo. The effect of ETHE1 on TNBC cell migratory potential was independent of its enzymatic activity. Mechanistic investigations revealed that ETHE1 interacted with eIF2α and enhanced its phosphorylation by promoting the interaction between eIF2α and GCN2. Phosphorylated eIF2α in turn upregulated the expression of ATF4, a transcriptional activator of genes involved in cell migration and tumor metastasis. Notably, inhibition of eIF2α phosphorylation through ISRIB or ATF4 knockdown partially abolished the tumor-promoting effect of ETHE1 overexpression. ETHE1 has a functional and mechanistic role in TNBC metastasis and offers a new therapeutic strategy for targeting ETHE1-propelled TNBC using ISRIB.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/patología , Factor 2 Eucariótico de Iniciación/metabolismo , Línea Celular Tumoral , Transducción de Señal , Proliferación Celular/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Mitocondriales/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo
16.
Chem Sci ; 14(40): 11170-11179, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37860665

RESUMEN

A catalyst-free photosensitized strategy has been developed for regioselective imino functionalizations of alkenes via the formation of an EDA complex. This photo-induced protocol facilitates the construction of structurally diverse ß-imino sulfones and vinyl sulfones in moderate to high yields. Mechanistic studies reveal that the reaction is initiated with an intermolecular charge transfer between oximes and sulfinates, followed by fragmentation to generate a persistent iminyl radical and transient sulfonyl radical. This catalyst-free protocol also features excellent regioselectivity, broad functional group tolerance and mild reaction conditions. The late stage functionalization of natural product derived compounds and total synthesis of some bioactive molecules have been demonstrated to highlight the utility of this protocol. Meanwhile, the compatibility of different donors has proved the generality of this strategy.

17.
Front Nutr ; 10: 1241580, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37693241

RESUMEN

In this paper, we study the effect of microbial fermentation on the nutrient composition and flavor of sweet potato slurry, different strains of Aspergillus niger, Saccharomyces cerevisiae, Lactobacillus plantarum, Bacillus coagulans, Bacillus subtilis, Lactobacillus acidophilus, and Bifidobacterium brevis were employed to ferment sweet potato slurry. After 48 h of fermentation with different strains (10% inoculation amount), we compared the effects of several strains on the nutritional and functional constituents (protein, soluble dietary fiber, organic acid, soluble sugar, total polyphenol, free amino acid, and sensory characteristics). The results demonstrated that the total sugar level of sweet potato slurry fell significantly after fermentation by various strains, indicating that these strains can utilize the nutritious components of sweet potato slurry for fermentation. The slurry's total protein and phenol concentrations increased significantly, and many strains demonstrated excellent fermentation performance. The pH of the slurry dropped from 6.78 to 3.28 to 5.95 after fermentation. The fermentation broth contained 17 free amino acids, and the change in free amino acid content is closely correlated with the flavor of the sweet potato fermentation slurry. The gas chromatography-mass spectrometry results reveal that microbial fermentation can effectively increase the kinds and concentration of flavor components in sweet potato slurry, enhancing its flavor and flavor profile. The results demonstrated that Aspergillus niger fermentation of sweet potato slurry might greatly enhance protein and total phenolic content, which is crucial in enhancing nutrition. However, Bacillus coagulans fermentation can enhance the concentration of free amino acids in sweet potato slurry by 64.83%, with a significant rise in fresh and sweet amino acids. After fermentation by Bacillus coagulans, the concentration of lactic acid and volatile flavor substances also achieved its highest level, which can considerably enhance its flavor. The above results showed that Aspergillus niger and Bacillus coagulans could be the ideal strains for sweet potato slurry fermentation.

18.
World J Oncol ; 14(4): 246-254, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37560338

RESUMEN

Background: The F-box protein 43 (FBXO43), also referred to as endogenous meiotic inhibitor 2 (EMI2), has been linked to the advancement of various types of cancer, such as hepatocellular carcinoma, breast cancer, cholangiocarcinoma, and gastric cancer. Nevertheless, the precise function of FBXO43 in colorectal cancer (CRC) remains unclear. This study employed data from The Cancer Genome Atlas (TCGA) and clinical specimens to analyze the expression, prognostic value, and chemotherapeutic advantages of FBXO43 in CRC. Methods: Level 3 RNA sequencing data pertaining to 631 cases of colon and rectal adenocarcinomas (COAD-READ) were downloaded from TCGA. The data were utilized to analyze the expression, prognosis, and related signal pathways of FBXO43. The expression of FBXO43 in clinical samples was subsequently confirmed through the use of real-time quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Lastly, a tissue microarray (TMA) consisting of 120 cases of CRC and corresponding normal tissues was established to investigate the relationship between FBXO43 and survival outcomes. Results: Results from both the TCGA analysis and clinical samples indicated that FBXO43 was significantly upregulated in CRC tissues in comparison to normal tissues. Moreover, high level of FBXO43 was found to be relevant to malignant clinical features, such as differentiation, lymph node metastasis, and pathological stage, as well as unfavorable prognosis in CRC patients. Subgroup analysis further demonstrated that FBXO43 could be an effective parameter for stratifying low-risk CRC patients. Notably, survival analysis showed that patients with high level of FBXO43 had worse overall survival (OS) and disease-free survival (DFS) following adjuvant chemotherapy, and FBXO43 was distinctly upregulated in chemotherapy-resistant patients' primary CRC tissues. Conclusions: FBXO43 was upregulated and associated with poor prognosis of CRC; patients with high expression of FBXO43 may not be benefit from adjuvant chemotherapy.

19.
Cardiovasc Ultrasound ; 21(1): 12, 2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37464361

RESUMEN

BACKGROUND: Conventional approach to myocardial strain analysis relies on a software designed for the left ventricle (LV) which is complex and time-consuming and is not specific for right ventricular (RV) and left atrial (LA) assessment. This study compared this conventional manual approach to strain evaluation with a novel semi-automatic analysis of myocardial strain, which is also chamber-specific. METHODS: Two experienced observers used the AutoStrain software and manual QLab analysis to measure the LV, RV and LA strains in 152 healthy volunteers. Fifty cases were randomly selected for timing evaluation. RESULTS: No significant differences in LV global longitudinal strain (LVGLS) were observed between the two methods (-21.0% ± 2.5% vs. -20.8% ± 2.4%, p = 0.230). Conversely, RV longitudinal free wall strain (RVFWS) and LA longitudinal strain during the reservoir phase (LASr) measured by the semi-automatic software differed from the manual analysis (RVFWS: -26.4% ± 4.8% vs. -31.3% ± 5.8%, p < 0.001; LAS: 48.0% ± 10.0% vs. 37.6% ± 9.9%, p < 0.001). Bland-Altman analysis showed a mean error of 0.1%, 4.9%, and 10.5% for LVGLS, RVFWS, and LASr, respectively, with limits of agreement of -2.9,2.6%, -8.1,17.9%, and -12.3,33.3%, respectively. The semi-automatic method had a significantly shorter strain analysis time compared with the manual method. CONCLUSIONS: The novel semi-automatic strain analysis has the potential to improve efficiency in measurement of longitudinal myocardial strain. It shows good agreement with manual analysis for LV strain measurement.


Asunto(s)
Ventrículos Cardíacos , Programas Informáticos , Humanos , Reproducibilidad de los Resultados , Estudios de Factibilidad , Ventrículos Cardíacos/diagnóstico por imagen , Atrios Cardíacos , Función Ventricular Izquierda
20.
ACS Omega ; 8(25): 23044-23050, 2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37396258

RESUMEN

A kind of organosilicon intermediate was prepared using isophorone diisocyanate (IPDI), hydroxyl silicone oil (HSO), and hydroxyethyl acrylate (HEA). The organosilicon modification of epoxy resin was realized by introducing a -Si-O- group into the side chain of epoxy resin by chemical grafting. The effects of organosilicon modification of epoxy resin on the mechanical properties systematically discuss its heat resistance and micromorphology. The results indicate that the curing shrinkage of the resin was decreased and the printing accuracy was improved. At the same time, the mechanical properties of the material are enhanced; the IS and elongation at break (EAB) are enhanced by 32.8 and 8.65%, respectively. The brittle fracture is changed to a ductile fracture, and the tensile strength (TS) of the material is decreased. The glass transition temperature (GTT) of the modified epoxy resin increased by 8.46 °C, and T50% and Tmax increased by 1.9 and 6 °C, respectively, indicating that the heat resistance of the modified epoxy resin was improved.

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